Under the leadership of Dr. Adrian Wiestner and the steering committee (Drs. Mark Knepper, Warren Leonard, Keji Zhao), the DIR DNA Sequencing and Genomics Core (DSGC) has been providing a wide spectrum of high-throughput genomics services to facilitate basic and translational research at NHLBI and across the NIH. (1) Consultation and data acquisition: the DSGC has provided the state-of-the-art genomics services for DIR investigators in a cost-effective and timely fashion. Diverse projects have been carried out including whole-genome sequencing, exome sequencing, transcriptome sequencing (RNA-seq and small RNA sequencing), MitoRCA-seq, targeted sequencing, ccf DNA sequencing, methyl-seq as well as single cell transcriptome analysis based on Fluidigm platform (2) In-depth data analysis: The DNA Sequencing and Genomics Core has explored and implemented a wide range of open-source and commercially available software packages for primary and secondary NGS data analysis. In addition, project-specific data analysis is further achieved by in-house software and algorithm development. As the result, it provides diverse tools for DIR investigators to convert the high-throughput data into biological meaningful findings for further characterization. (3) Training and education: The DSGC has taken all possible venues to promote broad dissemination of NGS technologies. Consultations are provided for experimental design and data analysis. The core also offers routine one-on-one training for library preparation and data analysis. (4) Research and development: Several R&D projects were carried out in collaboration with the DIR investigators. High priority was set for technologies that are beneficial to multiple users or expected to facilitate the broad applications of high-throughput sequencing platform. We have developed and optimized protocol for (a) mitoRCA-seq to identify single nucleotide mutations and indels related to aging and heart diseases (b) targeted sequencing assays for myeloid leukemia, pheochromocytomas, congenital heart disease (c) single-cell transcriptome analysis with Fluidigm C1 platform and an improved SPA-seq procedure; (d) cell-free DNA analysis for transplantation rejection and early detection of tissue damage. In addition, we have been developing computational pipelines and workflow for systematic identification of SNPs, alternative polyadenylation, global intron retention and other regulatory events in gene regulatory network (GRN).